LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1.

Abstract

Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but its role in idiopathic pulmonary fibrosis (IPF) is not fully understood. In this study, we found lncRNA Hoxaas3 (Hoxaas3) was up-regulated in the mice model of BLM-induced PF and TGF-β1-induced fibrogenesis in lung fibroblasts (LF). Overexpression of Hoxaas3 promoted fibrogenesis, whereas Hoxaas3 inhibition attenuated lung fibrosis both in vitro and in vivo, through regulation of miR-450b-5p. Furthermore, miR-450b-5p inhibition stimulated fibrogenesis by regulating runt-related transcription factor 1 (Runx1), whereas up-regulation of miR-450b-5p alleviated fibrogenesis in LF. Mechanistically, our study showed that Hoxaas3 regulated lung fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-450b-5p: Hoxaas3 decreased the expression of miR-450b-5p to stimulate level and activity of Runx1 and induced fibrotic LF, whereas Runx1 inhibition alleviated the pro-fibrotic effect of Hoxaas3. In addition, Hoxaas3 was regulated by TGF-β1/Smad4 pathway as its transcriptional target. In conclusion, our study showed the role and mechanism of the TGF-β1/Smad4- Hoxaas3-miR-450b-5p-Runx1 axis for a better understanding of PF, demonstrated Hoxaas3 maybe a new diagnostic biomarker or potential therapeutic target for IPF.

• Authors: Shuang Lin, Rui Zhang, Lei Xu, Rui Ma, Liming Xu, Linghua Zhu, Jian Hu, Xiaoxia An
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 8 Pg. 706 (08 26 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32848140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Core Binding Factor Alpha 2 Subunit
• Homeodomain Proteins
• MIRN450 microRNA, human
• MicroRNAs
• RNA, Antisense
• RNA, Long Noncoding
• RUNX1 protein, human
• Runx1 protein, mouse
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Bleomycin
• HoxA protein

Topics

• Animals
• Bleomycin (adverse effects)
• Cell Proliferation (drug effects)
• China
• Core Binding Factor Alpha 2 Subunit (genetics, metabolism)
• Fibroblasts (metabolism)
• Fibrosis (genetics, metabolism)
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Idiopathic Pulmonary Fibrosis (genetics)
• Lung (metabolism)
• Male
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• RNA, Antisense (genetics)
• RNA, Long Noncoding (genetics)
• Transforming Growth Factor beta1 (metabolism)